Background:
Ovarian cancer (OC) is the second most common gynecological malignancy and has a high mortality rate. The current chemotherapeutic drugs have the disadvantages of drug resistance and side effects. Myricetin, as a kind of natural medicine, has the advantages of easy extraction, low price, and few side effects. Numerous studies have demonstrated the anti-cancer properties of myricetin. However, the underlying effect of myricetin on ovarian cancer remains to be elaborated. Therefore, this study was aimed to application of in vivo and in vitro studies to reveal the mechanism of myricetin suppresses TGF-β-induced epithelial-to-mesenchymal (EMT) in OC.
Method:
n vitro experiments were conducted to evaluate the effects of myricetin on cell proliferation and apoptosis using CCK8 assay, plate clonal formation assay, and flow cytometry. The expression levels of caspase-3, PARP, and the MAPK/ERK and PI3K/AKT signaling pathways were assessed using western blotting. Wound healing and transwell, western blot and immunofluorescence assay were used to detect TGF-β-induced cell migration, invasion, EMT and the levels of Smad3, MAPK/ERK, PI3K/AKT signaling pathways. Additionally, a mouse xenograft model was established to verify the effects of myricetin on OC in vivo.
Results:
Myricetin inhibited the proliferation of ovarian cancer through MAPK/ERK and PI3K/AKT signaling pathways, promoted the apoptosis through the Caspase-3 and PARP signaling pathways in vitro and attenuated OC progression and metastasis in vivo. Moreover, myricetin reversed TGF-β-induced EMT through Smad3, MAPK/ERK and PI3K/AKT signaling pathway.
Conclusion:
Myricetin demonstrated inhibitory effects on OC progression and metastasis both in vivo and in vitro. It also reversed TGF-β-induced EMT through the classical and non-classical Smad signaling pathways.